TautomerCanonicalizer gives unexpected/forbidden form of phosphoric acid #20
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NADH looks like this original_smiles = 'NC(=O)C1=CN([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](N4C=NC5=C4N=CN=C5N)[C@H](O)[C@@H]3O)[C@@H](O)[C@H]2O)C=CC1'
original_mol = Chem.MolFromSmiles(original_smiles)
tautomerized_mol = TautomerCanonicalizer().canonicalize(original_mol)
Draw.MolsToGridImage([original_mol,tautomerized_mol],
molsPerRow=1,subImgSize=(600,300),
legends=['original','tautomer'])
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I think this is caused by the phosphonic acid rules: https://github.com/mcs07/MolVS/blob/master/molvs/tautomer.py#L130 It can probably be fixed by making the SMARTS pattern more strict to match only the intended target: |
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You are correct, removing that rule stops that moiety from being modified. When you say, "more strict", you think specify an explicit number of bonds on the Phosphorous in the SMARTS pattern? Why does rdkit allow 7 bonds on the phosphorous? Rdkit is a vast package, but looking at the definition of Phosphorous, it has max bonds of 5. If I do SantizeMol, the hydrogen stays put. When I paste the structure into ChemDraw, its not valid. |
gjgetzinger
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Apr 16, 2020
Updates SMARTS definitions for phosphinic acids. Requires 3 explicit (X3) and 3 total (D3) connections for tautomerizing phosphinic acids. New behavior properly handles compounds with 4 connections (e.g., phosphates, phosphonic acids).
```python
from rdkit import Chem
from molvs.tautomer import TautomerCanonicalizer
import pandas as pd
my_transforms = (
TautomerTransform('phosphonic acid f', '[OH]-[PD3X3H0]', bonds='='),
TautomerTransform('phosphonic acid r', '[PD3X3H1]=[O]', bonds='-')
)
cpds = ['methylphosphinic acid','methylphosphonous acid','methylphosphonic acid','NADPH']
smiles = ['CP(=O)O','CP(O)O','CP(=O)(O)O','NC(=O)C1=CN([C@@h]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@h](N4C=NC5=C4N=CN=C5N)[C@H](O)[C@@h]3O)[C@@h](O)[C@H]2O)C=CC1']
mols = [Chem.MolFromSmiles(smi) for smi in smiles]
can_taut = [TautomerCanonicalizer(transforms=my_transforms).canonicalize(mol) for mol in mols]
smiles_taut = [Chem.MolToSmiles(mol) for mol in can_taut]
df = pd.DataFrame({'cpd':cpds,'smi':smiles,'taut_smi':smiles_taut})
cpd smi taut_smi
0 methylphosphinic acid CP(=O)O C[PH](=O)O
1 methylphosphonous acid CP(O)O C[PH](=O)O
2 methylphosphonic acid CP(=O)(O)O CP(=O)(O)O
3 NADPH NC(=O)C1=CN([C@@h]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@h](N4C=NC5=C4N=CN=C5N)[C@H](O)[C@@h]3O)[C@@h](O)[C@H]2O)C=CC1 NC(=O)C1=CN([C@@h]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@h](n4cnc5c(N)ncnc54)[C@H](O)[C@@h]3O)[C@@h](O)[C@H]2O)C=CC1
```
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I'm converting all the molecules in my database to canonical-tautomers and noticed that things like NADH looked weird. You can see it most plainly for phosphoric acid. I didn't expect the Hydrogen on the phosphorous. Is this the correct/expected behavior?
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